Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis
Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis
Data
2019
Autores
Di Tanna, Gian Luca
Khaki, Ali Raza
Theron, Grant
McCarthy, Kerrigan
Cox, Helen
Mupfumi, Lucy
Trajman, Anete
Zijenah, Lynn Sodai
Mason, Peter
Bandason, Tsitsi
Journal Title
Journal ISSN
Volume Title
Publisher
The Lancet Global Health
Resumo
Background Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is
available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in
patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine
improvements in patient outcomes associated with Xpert MTB/RIF.
Methods We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to
Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy
as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary
tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis
and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause
mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for
multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or
random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and
previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number
CRD42014013394.
Findings Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees
(4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with
Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and
middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported
in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the
smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05
[p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs
16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI
0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was
low (I2<20% for the primary outcome).
Interpretation Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule
out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in
mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact.
Funding US National Institutes of Health.
Description
Palavras-chave
Adult, Antitubercular Agents / therapeutic use, Brazil / epidemiology, Cause of Death, Female, HIV Infections / epidemiology, Humans, Male, Middle Aged, Mortality, Mycobacterium tuberculosis / genetics*, Mycobacterium tuberculosis / isolation & purification, Nucleic Acid Amplification Techniques*, Odds Ratio, Outcome Assessment, Health Care, Proportional Hazards Models, South Africa / epidemiology, Sputum / microbiology*, Tanzania / epidemiology, Time-to-Treatment / statistics & numerical data, Tuberculosis, Pulmonary / diagnosis*, Tuberculosis, Pulmonary / drug therapy, Tuberculosis, Pulmonary / epidemiology, Tuberculosis, Pulmonary / mortality, Zambia / epidemiology, Zimbabwe / epidemiology
Citação
Di Tanna GL, Khaki AR, Theron G, McCarthy K, Cox H, Mupfumi L, Trajman A, Zijenah LS, Mason P, Bandason T, Durovni B, Bara W, Hoelscher M, Clowes P, Mangu C, Chanda D, Pym A, Mwaba P, Cobelens F, Nicol MP, Dheda K, Churchyard G, Fielding K, Metcalfe JZ. Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis. Lancet Glob Health. 2019 Feb;7(2):e191-e199. doi: 10.1016/S2214-109X(18)30458-3. Erratum in: Lancet Glob Health. 2019 Apr;7(4):e419. doi: 10.1016/S2214-109X(19)30046-4.